← All People

Margaret E. Glasner

Glasner, Margaret E.
Margaret E. Glasner
Associate Professor of Biochemistry and Biophysics
BioBio / Room 237A
Undergraduate Education
B.S., B.M. University of Wyoming (1995)
Graduate Education
Postdoc. University of California, San Francisco (2003-2008)
Joined Texas A&M in 2008
NSF CAREER Award 2013

Evolution of Protein Structure and Function

Evolution is the organizing principle of biology and provides the cornerstone of our approach to understand the relationships between protein structure and function. We combine bioinformatics, biochemistry, and genetics to address fundamental questions about protein evolution, such as: What structural and mechanistic features of enzymes increase their capacity to evolve new functions? How do new metabolic pathways evolve? Are there multiple evolutionary pathways to evolve new enzyme activities?

Our primary focus is on how catalytic promiscuity serves as the raw material for evolving new enzyme activities. Catalytic promiscuity is the ability to catalyze different chemical reactions using the same active site. Many enzymes in one branch of the protein family we are studying are catalytically promiscuous, and this activity has been incorporated into new metabolic pathways more than once. Comparing the sequences and structures of these proteins will identify characteristics that permitted them to evolve the second activity.

Our goal is to use results from our research to identify fundamental evolutionary principles that can can help decipher protein structure-function relationships, predict protein functions, and improve protein engineering methods.

Recent Publications

  1. Glasner, ME, Truong, DP, Morse, BC. How enzyme promiscuity and horizontal gene transfer contribute to metabolic innovation. FEBS J. 2020;287 (7):1323-1342.
    doi: 10.1111/febs.15185. PubMed PMID:31858709. PubMed Central PMC7245361.

  2. Burroughs, AM, Glasner, ME, Barry, KP, Taylor, EA, Aravind, L. Oxidative opening of the aromatic ring: Tracing the natural history of a large superfamily of dioxygenase domains and their relatives. J. Biol. Chem. 2019;294 (26):10211-10235.
    doi: 10.1074/jbc.RA119.007595. PubMed PMID:31092555. PubMed Central PMC6664185.

  3. Odokonyero, D, McMillan, AW, Ramagopal, UA, Toro, R, Truong, DP, Zhu, M et al.. Comparison of Alicyclobacillus acidocaldarius o-Succinylbenzoate Synthase to Its Promiscuous N-Succinylamino Acid Racemase/ o-Succinylbenzoate Synthase Relatives. Biochemistry. 2018;57 (26):3676-3689.
    doi: 10.1021/acs.biochem.8b00088. PubMed PMID:29767960. PubMed Central PMC7187728.

  4. Glasner, ME. Finding enzymes in the gut metagenome. Science. 2017;355 (6325):577-578.
    doi: 10.1126/science.aam7446. PubMed PMID:28183934. .

  5. McMillan, AW, Lopez, MS, Zhu, M, Morse, BC, Yeo, IC, Amos, J et al.. Role of an active site loop in the promiscuous activities of Amycolatopsis sp. T-1-60 NSAR/OSBS. Biochemistry. 2014;53 (27):4434-44.
    doi: 10.1021/bi500573v. PubMed PMID:24955846. .

  6. Brizendine, AM, Odokonyero, D, McMillan, AW, Zhu, M, Hull, K, Romo, D et al.. Promiscuity of Exiguobacterium sp. AT1b o-succinylbenzoate synthase illustrates evolutionary transitions in the OSBS family. Biochem. Biophys. Res. Commun. 2014;450 (1):679-84.
    doi: 10.1016/j.bbrc.2014.06.034. PubMed PMID:24937446. .

  7. Odokonyero, D, Sakai, A, Patskovsky, Y, Malashkevich, VN, Fedorov, AA, Bonanno, JB et al.. Loss of quaternary structure is associated with rapid sequence divergence in the OSBS family. Proc. Natl. Acad. Sci. U.S.A. 2014;111 (23):8535-40.
    doi: 10.1073/pnas.1318703111. PubMed PMID:24872444. PubMed Central PMC4060685.

  8. Odokonyero, D, Ragumani, S, Lopez, MS, Bonanno, JB, Ozerova, ND, Woodard, DR et al.. Divergent evolution of ligand binding in the o-succinylbenzoate synthase family. Biochemistry. 2013;52 (42):7512-21.
    doi: 10.1021/bi401176d. PubMed PMID:24060347. PubMed Central PMC3908897.

  9. Zhu, WW, Wang, C, Jipp, J, Ferguson, L, Lucas, SN, Hicks, MA et al.. Residues required for activity in Escherichia coli o-succinylbenzoate synthase (OSBS) are not conserved in all OSBS enzymes. Biochemistry. 2012;51 (31):6171-81.
    doi: 10.1021/bi300753j. PubMed PMID:22775324. .

  10. Sakai, A, Fedorov, AA, Fedorov, EV, Schnoes, AM, Glasner, ME, Brown, S et al.. Evolution of enzymatic activities in the enolase superfamily: stereochemically distinct mechanisms in two families of cis,cis-muconate lactonizing enzymes. Biochemistry. 2009;48 (7):1445-53.
    doi: 10.1021/bi802277h. PubMed PMID:19220063. PubMed Central PMC2746992.

Search PubMed